Neuropharmacology

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Terms in this set (...)

Central Nervous System (CNS) Drugs
Agents that act on the brain and spinal cord
CNS Drugs: Medical Uses
-Relief of pain
-Suppression of seizures
-Production of anesthesia
-Treatment of psychiatric disorders (not in this lecture)
CNS Drugs: Non medical Uses
Stimulant, depressant, euphoriant, and other "mind-altering" abilities
Parkinson's Disease
-Parkinson's disease (PD) is a neurodegenerative disorder of the extrapyramidal system associated with the disruption of neurotransmission in the striatum
-Neurotransmitters: Imbalance between Dopamine and acetocoline, this causes degeneration of neurotransmitters
-No cure for motor symptoms that occur

*Too little dopamine, too much acetylcholine
*Goal of drug therapy: Improve functional mobility and quality of life
Goal of Parkinson's drugs
-Restore functional balance between dopamine and acetylcholine

1. Dopaminergic agents: drugs that directly or indirectly activate dopamine receptors
2. Anticholinergic agents: drugs that block receptors for acetylcholine
Parkinson's Drugs
-Levodopa/Carbidopa
-Pramipexole
-Entacapone
-Selegiline
Levodopa/Carbidopa (Sinemet) MOA
Parkinson's Drug
-2 drugs in 1 pill
-MOA: carbidopa enhances effects of levodopa (no effects on its own, can't cross BBB)
-MOA: levodopa reduces symptoms of PD by increasing dopamine synthesis in the striatum (Promotes dopamine synthesis), crosses BBB through active transport

PO

*Most effective for PD
How Carbidopa helps Levodopa
-Carbidopa inhibits decarboxylation of levodopa in the intestine and peripheral tissues (makes levodopa more available to CNS)
-Carbidopa does not prevent conversion of levodopa to dopamine (carbidopa unable to cross BBB)
-Carbidopa helps reduce cardiovascular problems and NV related to Levodopa use (caused by production of dopamine in the periphery)
-Causes direct inhibition of decarboxylase, carbidopa eliminates concerns about decreasing the effects of levodopa - no need to take pyridoxine a vitamin preparation
Levodopa/Carbidopa [Sinemet]: Adverse Effects
DYSKINESIA
-Carbidopa has no adverse effects of its own
-Combined drug (Sinemet) can have abnormal movements and psychiatric disturbances
Levodopa/Carbidopa [Sinemet]: Dosing
Dosing:
-Available in immediate release (IR) and controlled release (CR)
-Dosage is low initially with gradual increase
*Takes several months to see effects
Levodopa/Carbidopa [Sinemet]: Precautions, interactions, and assessments
-Avoid high protein diets impair the absorption of levedopa
-Levodopa and other drugs: Drug interactions can increase or decrease or cause toxicity
-Labs to monitor - hepatic function, BUN, Creat, CBC
-Pregnancy category C drug
Pramipexole [Mirapex]
Parkinson's Drug
-Dopamine Agonists: non-ergot dopamine receptor agonist
-Used alone in early PD and with levodopa in advancing PD
-Maximal benefits take several weeks to develop
* Less effective with Sinemet
-Lower incidence of treatment failure
-Less likely to cause dyskinesia
-Not going to hurt the liver

PO

*Also used for RLS
Pramipexole [Mirapex]: Adverse Effects
-Monotherapy: Nausea, dizziness, daytime somnolence, insomnia, constipation, weakness, and hallucinations, "sleep attacks": extreme sleepiness without warning
-Combined: Orthostatic hypotension, dyskinesias, and increase in hallucinations
-Rare instances of pathologic gambling and other compulsive self-rewarding behaviors
Entacapone [Comtan]
Parkinson's Drug
-COMT Inhibitor (class)
-Keeps Levdopa from wearing off
-Selective and reversible inhibitor of COMT
-Indicated for use with LEVODOPA
-Inhibits metabolism of levodopa in the intestines and the peripheral tissues
-Prolongs time that levodopa is available to the brain
-Increases levodopa availability by inhibiting COMT, which decreases the production of levodopa metabolites that compete with levodopa for transport

PO
Entacapone [Comtan]: Adverse effects and interactions
*Occur from increasing levels of Levodopa
Adverse Effects:
-dyskinesias
-Orthostatic hypotension
-Hallucinations
-NV
-Discolored urine

Drug to drug interactions:
-Antihypertensives
-Cardiac drugs
What is a COMT inhibitor???
-Dopaminergic agent
-Inhibitors of COMT enhance the effects of Levodopa by blocking its degradation (so that dopamine can be released and breakdown of it can be prevented)
-Inhibits metabolism of Levodopa in the periphery
Selegiline [Eldepryl, Zelapar]
Parkinson's Drug
MAO-B Inhibitor (class)
-Used in newly diagnosed patients for managing off times during Levodopa therapy
-Monotherapy or used with levodopa
-Modest improvement in motor function
-Causes selective and irreversible inhibition of MAO-B
-Can suppress the destruction of dopamine derived from levodopa and prolong the effects of levodopa
-Benefits decline dramatically within 12 to 24 months

PO

MOA: Help block breakdown of dopamine in brain, reduce motor symptoms
Selegiline [Eldepryl, Zelapar]:Adverse Effects
-Insomnia
-Orthostatic hypotension
-Dizziness
-GI problems
-Irritation of the buccal mucosa
Selegiline [Eldepryl, Zelapar]: Drug Interactions
-Meperidine
-SSRIs
MOA-B Inhibitor????
-Dopaminergic agent
-Activate dopamine receptors
-Inhibitors of MAO-B prevent dopamine breakdown
-Amantadine promotes dopamine relaease
Alzheimer's Disease
-Devastating illness
-Progressive memory loss
-Impaired thinking
-Neuropsychiatric symptoms
-Inability to perform routine tasks of daily living
-Alzheimer's disease (AD) affects more than 5 million Americans
-Sixth leading cause of death in the United States

Patho:
-Degeneration of neurons: Early in hippocampus (Memory)
-Later in cerebral cortex: Speech, perception, reasoning, and other higher functions
Subsequent decline in cerebral volume

Symptoms:
Memory loss, Confusion, Feeling disoriented, Impaired judgment , Personality changes, Difficulty with self-care, depression, aggression, hyper sexuality
Drugs for Cognitive Impairment
-Goal of AD treatment is to improve symptoms and reverse cognitive decline

-Currently available drugs cannot do this

-Drugs now in use may slow loss of memory and cognition and prolong independent function; however, for many patients, even these modest goals are elusive
Drug Therapy for AD
-Donepezil [Aricept, Aricept ODT]
-Memantine [Namenda, Namenda XR]
Donepezil [Aricept, Aricept ODT]
Alzheimer's Drug
-Cholinesterase inhibitor
-Indicated for mild, moderate, or severe AD
-Causes reversible inhibition of cholinesterase: increase the acetocoline in the brain and heart
-Metabolized by P450 enzyme

PO
Donepezil [Aricept, Aricept ODT]: Adverse Effects and Assessments
Adverse effects:
-Nausea and diarrhea
-Bradycardia
-Fainting
-Falls*
-Fall-related fractures

Assess: HR, BP
Memantine [Namenda, Namenda XR]
Alzheimer's Drug
-First drug in a new class, the N-methyl-d-aspartate receptor antagonists NDMA
-Indicated for moderate to severe AD*
-Better tolerated than cholinesterase inhibitors

-MOA: Modulates the effects of glutamate at the NDMA receptors which are believed to play a critical role in learning and memory
-Blocks calcium influx when glutamate is low and permits it when glutamate is high

PO
Memantine [Namenda, Namenda XR]: Adverse Effects
Adverse effects:
-Dizziness (falls)
-Headache
-Confusion
-Constipation
Patient with AD might be on
Antipsychotic drugs (risparetol, driprexa)
Epilepsy
-Group of disorders characterized by excessive excitability of neurons in the central nervous system
-Can produce a variety of symptoms that range from brief periods of unconsciousness to violent convulsions
-May also cause problems with learning, memory, and mood
-Can have many different types of seizures
Epilepsy: Therapeutic Considerations
-Monitoring plasma drug levels to make sure pt is at a therapeutic range
-Promoting patient adherence
-Withdrawing antiepileptic drugs
-Suicide risk: Antiepileptic drugs
Antiepileptic Drugs (AED)
-Phenytoin
-Carbamazepine
-Valproic Acid
-Phenobarbital
-Gabapentin

Goal: Decrease incidence of seizures
1. Suppress discharge of neurons within a seizure focus
2. Suppress propagation of seizure activity from the focus to other areas of the brain

-Older AEDs are less well tolerated, cause more fetal damage, and have more drug interactions

*A lot of these drugs can be given for bipolar disorder or neuropathic pain
Phenytoin [Dilantin]
AED
1st drug to suppress seizures without suppressing the entire CNS
-Partial and tonic-clonic seizures
-MOA: Selective inhibition of sodium channels
-Surpasses activity of seizure generating neurons while leaving healthy neurons unaffected

-Varied oral absorption
-Half-life: 8 to 60 hours
-Therapeutic levels: 10 to 20 mcg/mL

*Can be given IV to treat SE and also used to treat cardiac dysrhythmias
Phenytoin [Dilantin]: Adverse Effects
-Nystagmus
-Sedation
-Ataxia
-Diplopia (double vision)
-Cognitive impairment
-Gingival hyperplasia (swelling gums, folic acid 0.5 mg per day can prevent gum overgrowth)
-Skin rash (steven Johnson's syndrome or toxic epidermal necrolysis)
-Effects in pregnancy
-Cardiovascular effects
-Suicidal thoughts

-When given IV: can cause cardiac dysrhythmias and hypotension (inject slowing and always dilute, VESICANT)
-Purple glove syndrome
Phenytoin [Dilantin]: Interactions, dosing, administration
Drug interactions:
-Decreases the effects of oral contraceptives (orthotrycycline, pt get pregnant), warfarin (bleeding), and glucocorticoids
-Increases levels of diazepam, isoniazid, cimetidine, alcohol, and valproic acid

-Dosing: Highly individualized
-Administration: With food
*Small increases in doses can cause toxicity and small decreased in toxicity can cause therapeutic failure
Carbamazepine [Tegretol]
AED
Uses:
-Epilepsy: Partial and tonic clonic
-Bipolar disorder
-Trigeminal and glossopharyngeal neuralgias

Mechanism of action:
-Suppresses high-frequency neuronal discharge in and around seizure foci (similar to phenytoin, delayed recovering of sodium channels from their inactivated site)

*Obtain blood counts before treatment
Carbamazepine [Tegretol]: Adverse effects, interactions, precautions
Adverse effects: (Fewer than phenytoin)
-Neurologic effects: Nystagmus* (Early sign) and ataxia
-Hematologic effects: Leukopenia, anemia, and thrombocytopenia
-Birth defects
-Hypo-osmolarity
-Dermatologic effects: Rash and photosensitivity reactions
-Monitor sodium level
-Can cause water retention
-Petechiae

Interactions: Warfarin, birth control, phenobarbital, grape fruit juice

*NOT for pregnant women, D
Valproic Acid [Depakene, Depakote, Depacon]
AED
Mechanism of action:
-Suppresses high-frequency neuronal firing through the blockade of sodium channels
-Suppresses calcium influx through T-type calcium channels
-May augment the inhibitory influence of GABA
-Partial, tonic-clonic, absence, and myoclonic seizures

PO or IV

*Also prescribed for migraines and bipolar disorder
Valproic Acid [Depakene, Depakote, Depacon]: Adverse effects
Adverse effects:
-Minimal sedation and cognitive impairment
-GI
-Heptatoxicity
-Pancreatitis
-NV
-Hyperammonemia (excess amonia in blood)
-Rash, hair loss, tremors
-Leukopenia, thrombocytopenia, blood cell aplasia
-Highly tetrogenic, D
Valproic Acid [Depakene, Depakote, Depacon]: Drug interactions
-Phenobarbital
-Phenytoin
-Topirmate
-Carbapenem antibiotics
Phenobarbital
-Anti-convuslant Barbiturate (it can reduce seizures without causing sedation like other barbiturates)
-MOA: Potentiates the effects of GABA

Uses:
-Epilepsy (partial and tonic clonic)
-Sedation
-Induction of sleep

-Risk for physical dependence
-PO, IV (for SE, vesicant), and IM
*One of the oldest AEDs
Phenobarbital: Adverse Effects and interactions
Adverse effects:
-Lethargy
-Depression
-Learing impairment
-Drowziness
-Not for pregnant women
-Rickets and osteomalcacia
-Nystagmus
-Ataxia

Interactions:
-CNS depressants (alcohol, benzos, opioids)
-Valporic acid
Gabapentin [Neurontin, Gralise]
AED
-Therapeutic use: Adjunctive therapy of partial seizures
-Off-label use: Neuropathic pain, prophylaxis of migraine, treatment of fibromyalgia, and relief of postmenopausal hot flashes
-Fewer Drug interaction compared to other drugs

Side effects: somnolence (prolonged drowsiness), dizziness, ataxia, fatigue, peripheral edema

PO
*Really popular
Management of Generalized Convulsive Status Epilepticus
-Continuous series of tonic-clonic seizures that lasts 20 to 30 minutes
-Give Lorazepam (Ativan) or Valium first** (benzos)

Goals of treatment:
-Maintain ventilation
-Correct hypoglycemia
-Terminate seizures
-Initiate or continue long-term suppression drugs such as phenytoin [Dilantin] or fosphenytoin [Cerebyx]
Sedative-Hypnotic Drugs
-Drugs that depress central nervous system (CNS) function
-Primarily used to treat anxiety and insomnia
-Antianxiety agents or anxiolytics
-Distinction between antianxiety effects and hypnotic effects is often a matter of dosage
Benzodiazepines Use
Therapeutic uses:
-Anxiety
-Insomnia
-Seizure disorders
-Muscle spasm
-Alcohol withdrawal
-Perioperative applications

Schedule 4

*Can be used for IV induction
Benzos as preoperative meds
1. Calm the patient
2. Provide analgesia
3. Counteract adverse effects of general anesthetics
Benzodiazepines Adverse effects
-CNS depression
-Anterograde amnesia (inability to remember recent memories)
-Sleep driving
-Respiratory depression
-Abuse
-Use in pregnancy and lactation (lethargy and weight loss in infant, category D)

Acute toxicity: PO only
-Drowsiness
-Lethargy
-Confusion
Flumazenil
-Not tested on but might be on NCLEX
-Antidote for overdose of benzos
Benzodiazepines Drug interactions and tolerance/ dependence
Drug interactions:
-CNS depressants
-Opioids

Tolerance and physical dependence
-Tolerance: With prolonged use, tolerance develops to some effects but not others

-Physical dependence: Can cause physical dependence, but the incidence of substantial dependence is low
Zolpidem [Ambien]
-Benzodiazepine-like Drugs
-Sedative-hypnotic
-Most widely used hypnotic
-Short-term management of insomnia
-Long term use: No apparent tolerance or increase in adverse effects
-Side effects: Daytime drowsiness and dizziness
-Should only take for 10 days
Anesthetics
-Local
-Lidocaine
-Isoflurane
-Propofol
Local Anesthetics
-Suppress pain by blocking sodium channels and by blocking impulse conduction along axons
-Only in neurons located near the site of administration
-Suppress pain without generalized depression of nervous system
-No respiratory depression
-Use with vasoconstrictors Epi
Epinephrine with local anesthetics
-Epinephrine: Decreases local blood flow, delays systemic absorption of the anesthetic, prolongs anesthesia, and reduces the risk of toxicity

*if given on digit, ear, or tip of nose you can lose circulation on that part of your body (gangrene)

Adverse effects:
-Absorption of the vasoconstrictor itself can result in systemic toxicity:
-Palpitations
-Tachycardia
-Nervousness
-Hypertension
Lidocaine
Anesthetic
-Most widely used local anesthetic
-Topical and injectable applications
-Effects extended if given with epinephrine
-Also used for cardiac dysrhythmias

-Preparations: Cream, Ointment, Jelly, Solution, Aerosol, Patch (wear gloves)
Lidocaine: Adverse Effects and Precautions
Adverse effects:
-Can effect a pt systemically (cardiac: bradycardia, can lead to heart block)
-Allergic reaction
-CNS excitation followed by depression

-Topical or Injection

*Pt should not wrap it in plastic or saran wrap, always use smallest amount as needed, don't apply it to a large surface area, don't apply to broken skin, don't want them to overheat or sweat in excess (Increases absorption which can cause CV problems)
General Anesthetics
-General anesthetics are drugs that produce unconsciousness and a lack of responsiveness to all painful stimuli
-Local anesthetics do not reduce consciousness, and they blunt pain only in a limited area
Basic Pharmacology of Inhalation Anesthetics
Properties of an ideal inhalation anesthetic:
-Unconsciousness
-Analgesia
-Muscle relaxation
-Amnesia
-Induction brief and pleasant
-Emergence brief and pleasant
-Depth of anesthesia raised or lowered with ease
-Minimal adverse effects
-Large margin of safety
Pharmacokinetics: Inhalation Anesthetics
Uptake and distribution:
-Uptake: From the lungs, The greater the concentration, the more rapid the uptake

-Distribution: To the CNS and other tissues, Determined largely by regional blood flow

Factors effecting distribution and uptake: Solubility of inhaled agents, pts cardiac output, gas exchange in alveoli

-Elimination: Exported in the expired breath, Inhalation anesthetics are almost entirely eliminated by the lungs

-Metabolism: Hepatic metabolism is minimal
Drug Interactions: Inhalation Anesthetics
-Analgesics, CNS depressants, and CNS stimulants can influence the amount of anesthetic required to produce anesthesia
-Opioids allow for a reduction
-CNS depressants add to the depressant effects of anesthesia
-Anti- anxiety meds
Isoflurane [Forane]
Anesthetic
-Prototype of the volatile inhalation anesthetics:
-Acts quickly
-Induction is usually produced with propofol
-When the patient is unconscious, depth of anesthesia can be raised or lowered with ease
-Patients awaken about 20 minutes after ceasing isoflurane inhalation
-Weak analgesic (may need to add an analgesic)
-Muscle relaxation inadequate for surgery
Isoflurane [Forane]: Adverse Effects
-Hypotension
-Respiratory depression: to ensure adequate oxygenation 2 things are implemented
1. Mechanical or manual ventilatory support
2. Enrichment of the inspired gas mixture with oxygen
-Nausea
-Vomiting
-Decreased urinary output
Pancuronium
-Not on test but might be on NCLEX
-Relaxes skeletal muscles during surgery
IV anesthetics
1. they permit dosage of the inhalation agent to be reduced
2. they produce effects that can't be achieved with an inhalation agent alone
Propofol
Most widely used IV anesthetic
Actions and uses:
-Unconsciousness develops within 60 seconds and lasts for 3 to 5 minutes
-Sedative-hypnotic for the induction and maintenance of analgesia
-Promotes the release of GABA in the brain causing CNS depression
-Mechanical ventilation and procedures
Propofol: Adverse Effects
-Narrow therapeutic range
-Can cause profound respiratory depression*** (monitor respiratory rate and rhythm)
-Can cause hypotension
-Risk of bacterial infection (drawing drug up from vile or pre-filled syringes)

-Pregnancy category B
Propofol: Risk for abuse
-Not a controlled substance
-Supplies are not closely monitored
-Widely available in operating rooms and other areas of hospitals and clinics
-No "high"
-Instantaneous but brief sleep period
-Patients awaken "refreshed" and talkative; many report feeling elated and even euphoric
Analgesics and Opioids
-Analgesics are drugs that relieve pain without causing the loss of consciousness
-Opioids are the most effective pain relievers available*
Pure Opioid Agonists
-Activate mu receptors and kappa receptors
-Can produce analgesia, euphoria, sedation, respiratory depression, physical dependence, constipation, and other effects
-Morphine: Strong opioid agonists and moderate to strong opioid agonists
-Codeine: Moderate to strong agonists
Analgesics and opioids: drugs
-Methylnaltrexone
-Morphine Sulfate
-Fentanyl
-Hyrdomorphone
-Codiene
-Hydrocodone
-Naloxone
-Tramadol
-Oxymorphone
-Levorphanol
Methylnaltrexone
Used to treat opioid-induced constipation
Morphine Sulfate
-Source: Seedpod of the poppy plant

Overview of pharmacologic actions:
-Pain relief
-Drowsiness
-Mental clouding
-Anxiety reduction
-Sense of well-being (euphoria)

MOA: Relieve pain by mimicking the actions of endogenous opioid peptides, primarily at the mu receptors

IV, IM, SQ, PO, Intrathecal

Schedule 2
Morphine Sulfate: Adverse Effects
-Respiratory depression
-Constipation
-Orthostatic hypotension
-Urinary retention and hesitancy
-Cough suppression
-Biliary colic
-Emesis
-Elevation of intracranial pressure
-Euphoria/dysphoria
-Sedation
-Miosis (dilated pupils: pinpoint)
-Neurotoxicity
-Hormonal changes
-Immune system problems
Morphine sulfate: pharmacokinetics
-Administered by several routes: oral, intramuscular, intravenous, subcutaneous, epidural, and intrathecal
-Not very lipid-soluble
-Does not cross blood-brain barrier easily
-Only small fraction of each dose reaches site of analgesic action
Morphine Sulfate: Tolerance/ dependence
Tolerance:
-Increased doses needed to obtain the same response
-Develops with analgesia, euphoria, sedation, and respiratory depression
-Cross-tolerance to other opioid agonists
-No tolerance to miosis or constipation develops
Morphine Sulfate: Drug Interactions
-CNS depressants
-Anticholinergic drugs
-Hypotensive drugs
-Monoamine oxidase inhibitors
-Agonist-antagonist opioids
-Opioid antagonists
-Other interactions
Morphine Sulfate: Toxicity
Clinical manifestations:
-Classic triad: Coma, Respiratory depression, Pinpoint pupils

Treatment:
-Ventilatory support
-Antagonist: Naloxone [Narcan]

General guidelines:
-Monitor vital signs before giving
-Give on a fixed schedule
Fentanyl [Duragesic, Abstral, Actiq, Fentora, Onsolis, Lazanda, Subsys]
-100 times the potency of morphine
-Formulations given via three routes

-Parenteral: Surgical anesthesia

-Transdermal [Duragesic]
Patch: Heat acceleration, Iontophoretic system: Needle-free

-Transmucosal: Lozenge on a stick [Actiq], Buccal film [Onsolis], Buccal tablets [Fentora], Sublingual tablets [Abstral], Sublingual spray [Subsys]

Schedule 2
oxymorphone and levorphanol ?
-Basic pharmacology
-Preparations, dosage, and administration
Hyrdomorphone
-Dilatid
-Very strong opiod
-Schedule 2
-Constipation, respiratory depression
*EMPTY stomach
Moderate to Strong Opioid Agonists
-Codiene and hydrocodone

Similar to morphine in most respects:
-Produce analgesia, sedation, and euphoria
-Can cause the following: Respiratory depression, constipation, urinary retention, cough suppression, and miosis
-Can be reversed with naloxone

Different from morphine:
-Produce less analgesia and respiratory depression than morphine
-Somewhat lower potential for abuse
Codiene
-Schedule II
-PO
-Cough suppressant
Hydrocodone
-Schedule III
-Most widely prescribed drug in the United States
-Combined with aspirin (limit 4,000 mg per day), acetaminophen, or ibuprofen
-Contraindicated: renal or liver disease
-Cough suppression
Moderate to Strong Opioid Agonists: Dosing Guidelines
Assessment of pain:
-Pain status should be evaluated before opioid administration and about 1 hour after

Dosage determination:
-Opioid analgesics must be adjusted to accommodate individual variation

Dosing schedule:
-As a rule, opioids should be administered on a fixed schedule

Avoiding withdrawal: always taper pt off drug
Opioid Antagonist Naloxone (Narcan)*
Mechanism of action: Competitive antagonist

*Can reverse the effect for ANY type of opioid
-Naloxone [Narcan]: Prototype of the pure opioid antagonists
-Antagonists at mu and kappa receptors
-Do not produce analgesia or any of the other effects caused by opioid agonists
-Reversal of respiratory and central nervous system (CNS) depression caused by overdose with opioid agonists

Therapeutic uses:
-Reversal of opioid overdose
(Drug of choice with pure opioid agonist overdose, Titrated cautiously with physical dependence)

-Reversal of postoperative opioid effects (Titrated to achieve adequate ventilation and to maintain pain relief)

-Reversal of neonatal respiratory depression (Opioids given during labor and delivery may cause respiratory depression in neonate)

*PAIN WILL COME BACK
Tramadol (Ultram)
Mechanism of action:
-Combination of opioid and nonopioid mechanisms (not true opioid drug)
-Blocks NE and serotonin
-Low potential of abuse, respiratory depression, and dependence
-Abuse liability: low

-Preparations, dosage, and administration: Immediate-release and extended-release
-Don't give to pts with seizures
-Schedule 4
Tramadol: Adverse Effects and Interacitons
Adverse effects:
-Sedation
-Dizziness
-Headache
-Dry mouth
-Constipation
-Seizures
-Suicide risk

-Drug interactions: CNS depressants, MOA inhibitors, SSRIs

-Don't give to pts with seizures
**If you give pt this drug and they're on SSRI they could get serotonin syndrome and DIE (increase in bp, hr, muscle twitching, heavy sweats, agitated)
Migraine Headache
Characteristics:
-Throbbing head pain of moderate to severe intensity
-Nausea and vomiting
Sensitivity to light and sound
-Highly debilitating

Patho:
-Neurovascular disorder that involves the dilation and inflammation of intracranial blood vessels
-Vasodilation leads to pain (give vasoconstrictor)
-Neurons of the trigeminal vascular system
-Calcitonin gene-related peptide (CGRP)
-Serotonin (5-hydroxytryptamine [5-HT])
Serotonin 1B/1D Receptor Agonists
Constrict intracranial blood vessels and suppress release of inflammatory neuropeptides
Sumatriptan [Imitrex]
Migraine Drug
-Serotonin 1B/1D Receptor Agonists

Mechanism of action:
-Binds to receptors on intracranial blood vessels and causes vasoconstriction*
-Diminishes perivascular inflammation

Therapeutic use:
-Aborting an ongoing migraine attack to relieve headache and associated symptoms

Pharmacokinetics:
-Oral, intranasal administration, SQ
Sumatriptan [Imitrex]: Adverse Effects
-Chest symptoms: Transient "heavy arms" or "chest pressure" experienced by 50% of users
-Coronary vasospasm: Rare angina as a result of vasospasm
-Teratogenesis: not for any body pregnant or considering becoming pregnant
-Others: Vertigo, malaise, fatigue, and tingling sensations, Very bad taste when taken in intranasal form
Sumatriptan [Imitrex]: Interactions and preparations
Drug interactions:
-Ergot alkaloids, sumatriptan, and other triptans (all cause vasoconstriction), MAOIs, SSRIs
Ergotamine
Migraine Drug
-Ergot alkaloids (class)
-Agonist activity at subtypes of serotonin receptors, specifically 5-HT1B and 5-HT1D receptors
-Suppresses release of CGRP to block inflammation associated with the trigeminal vascular system***
-In cranial arteries it acts directly to promote constriction and reduce amplitude of pulsations

-Second-line drug for stopping an ongoing migraine attack in patients who have not responded to a triptan
-Risk for dependence

-Toxicity: Ergotism (poisoning effect), hallucinations, NV, painful burning sensation to arms and legs (vasospasm)
-Drug interactions: Triptans, CYP3A4 inhibitors
-Physical dependence
Ergotamine: Adverse effects
-NV
-Leg weakness
-Myalgia
-Numbness or tingling in the fingers and toes
-Angina like pain
-Tachy or bradycardia
-Pregnancy category X
Migraines: Preventive Therapy
-Beta blockers: Propranolol, timolol, atenolol, metoprolol, and nadolol

-Antiepileptic drugs AED: Divalproex [Depakote ER], topiramate [Topamax], gabapentin [Neurontin], and tiagabine [Gabitril]

-Tricyclic antidepressants: Amitriptyline [Elavil]

-Estrogens and triptans for menstrually associated migraine: Estrogen gel and patches (for example, Climara, Estraderm), frovatriptan, naratriptan, zolmitriptan, and naproxen sodium